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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LHX8
LIM homeobox 8
Chromosome 1 · 1p31.1
NCBI Gene: 431707Ensembl: ENSG00000162624.17HGNC: HGNC:28838UniProt: Q68G74
40PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingprotein bindingRNA polymerase II transcription regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificskin agingobstructive sleep apneathrombophiliaWheezing
✦AI Summary

LHX8 is a LIM-homeobox transcription factor that functions as a cell fate regulator in multiple developmental contexts 1. In oogenesis, LHX8 operates within a transcriptional network with FIGLA and SOHLH1 to regulate oocyte growth, differentiation, and meiotic progression during early folliculogenesis 2. LHX8 mutations are associated with primary ovarian insufficiency (POI), a leading genetic cause of premature reproductive failure in women 3. In the ovary, LHX8 expression correlates with oocyte quality; nicotinamide mononucleotide treatment restores LHX8 expression in obesity-compromised oocytes 4. Beyond reproduction, LHX8 regulates craniofacial development by negatively controlling the cell cycle inhibitor p57(Kip2), promoting palatal development through mechanisms involving FOX family transcription factors 5. In dental mesenchyme, LHX8 modulates differentiation via Wnt and TGFβ pathways 6 and interacts with Suv39h1 to repress odontoblast differentiation genes through H3K9 methylation, balancing proliferation and differentiation 7. Clinically, LHX8 methylation status serves as a biomarker for cervical cancer screening in HIV-positive women, demonstrating diagnostic utility beyond developmental biology 8.

Sources cited
1
LHX8 is associated with non-syndromic primary ovarian insufficiency and implicated in ovarian development and meiosis/DNA repair pathways
PMID: 34794894
2
LHX8 is an ovary development-related gene whose expression is restored by nicotinamide mononucleotide treatment in obese mice
PMID: 35811338
3
LHX8 is a conserved LIM-homeobox transcription factor involved in cell fate specification in neurogenesis, craniofacial development, and germ cell differentiation
PMID: 26148970
4
LHX8 negatively regulates p57(Kip2) expression to promote palate development through both direct and indirect mechanisms involving FOX transcription factors
PMID: 26071365
5
LHX8 methylation serves as a biomarker for cervical cancer screening with high sensitivity and specificity
PMID: 36366827
6
LHX8 regulates dental mesenchyme differentiation and dentin development via Wnt and TGFβ pathway modulation
PMID: 26081866
7
LHX8 interacts with Suv39h1 to repress odontoblast differentiation genes through H3K9 methylation and is regulated by FGF8 and BMP2 signals
PMID: 33580754
8
LHX8 cooperates with FIGLA and SOHLH1 in transcriptional networks regulating oocyte maintenance, differentiation, and meiotic progression during early folliculogenesis
PMID: 32086523
Disease Associationsⓘ20
skin agingOpen Targets
0.41Moderate
obstructive sleep apneaOpen Targets
0.37Weak
thrombophiliaOpen Targets
0.29Weak
WheezingOpen Targets
0.27Weak
jaw diseaseOpen Targets
0.27Weak
orofacial cleftOpen Targets
0.18Weak
health study participationOpen Targets
0.18Weak
Cerebral degenerationOpen Targets
0.16Weak
contractureOpen Targets
0.09Suggestive
nephrotic syndromeOpen Targets
0.07Suggestive
primary ovarian insufficiencyOpen Targets
0.07Suggestive
46,XX gonadal dysgenesisOpen Targets
0.07Suggestive
spondylolisthesisOpen Targets
0.06Suggestive
Testicular regression syndromeOpen Targets
0.06Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.06Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.06Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.05Suggestive
Mayer-Rokitansky-Küster-Hauser syndromeOpen Targets
0.05Suggestive
lethal omphalocele-cleft palate syndromeOpen Targets
0.05Suggestive
central nervous system infectionOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GBX1Protein interaction90%MSX1Protein interaction85%YBX2Protein interaction85%NOBOXProtein interaction85%PAX9Protein interaction81%LDB1Protein interaction71%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
50%
Lung
0%
Ovary
0%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
LHX8GBX1MSX1YBX2NOBOXPAX9LDB1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q68G74
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.52Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.31 [0.20–0.52]
RankingsWhere LHX8 stands among ~20K protein-coding genes
  • #10,194of 20,598
    Most Researched40
  • #3,201of 17,882
    Most Constrained (LOEUF)0.52 · top quartile
Genes detectedLHX8
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab · 2022
1.00
2
Administration of nicotinamide mononucleotide improves oocyte quality of obese mice.
PMID: 35811338
Cell Prolif · 2022
0.90
3
PMID: 39637134
0.80
4
Lhx6 and Lhx8: cell fate regulators and beyond.
PMID: 26148970
FASEB J · 2015
0.70
5
Lhx6 and Lhx8 promote palate development through negative regulation of a cell cycle inhibitor gene, p57Kip2.
PMID: 26071365
Hum Mol Genet · 2015
0.60